Synthesis and Anti-HIV Activity of a Series of 6-Modified 2＇,3＇-Dideoxyguanosine and 2＇,3＇-Didehydro-2＇,3＇- dideoxyguanosine Analogs

In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile ＂one-pot＂ method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase （RT） incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.